Andersson B, Sylvén C
Division of Cardiology, the Wallenberg Laboratory for Cardiovascular Research, University Hospital, Göteborg, Sweden.
J Am Coll Cardiol. 1996 Jul;28(1):162-7. doi: 10.1016/0735-1097(96)00098-8.
The aim of the present study was to investigate the association between the homozygous DD (deletion) genotype of the angiotensin-converting enzyme gene and survival and cardiac function in patients with idiopathic congestive heart failure.
The DD genotype gene is a linkage marker for an etiologic mutation at or near the angiotensin-converting enzyme gene and has been associated with increased risk for the development of coronary artery disease, left ventricular hypertrophy and left ventricular dilation after myocardial infarction. We investigated the association between this angiotensin-converting enzyme genotype and mortality in a population-based cohort of patients with idiopathic congestive heart failure.
The genotype was determined in 193 patients recruited from a large unselected population of patients with congestive heart failure (n = 2,711). The patients were studied with echocardiography, and survival data were obtained after 5 years of follow-up. A control group from the general population (n = 77) was studied by a similar procedure.
The frequency of the D allele was not significantly different in the study and control groups (0.57 vs 0.56, p = NS). Long-term survival was significantly worse in the patients with the DD genotype than in the remaining patients (5-year survival rate 49% vs. 72%, p = 0.0011 as assessed by log rank test). The independent importance of the DD genotype for prognosis was verified by a multivariate Cox proportional hazards analysis, by which the odds ratio for mortality and the DD genotype was 1.69 (95% confidence interval 1.01 to 2.82). The only significant difference in cardiac function data between the two groups was an increase in left ventricular mass index in the DD group (153 +/- 57 vs 134 +/- 44 g/m2, p = 0.019).
Angiotensin-converting enzyme gene DD polymorphism was associated with poorer survival and an increase in left ventricular mass in patients with idiopathic heart failure. The results suggest a possible pathophysiologic pathway between angiotensin-converting enzyme gene polymorphism, angiotensin-converting enzyme activity, myocardial hypertrophy and survival. Therefore, the DD genotype may be a marker of poor prognosis in patients with congestive heart failure.
本研究旨在调查血管紧张素转换酶基因纯合子DD（缺失）基因型与特发性充血性心力衰竭患者生存率及心脏功能之间的关联。
DD基因型基因是血管紧张素转换酶基因或其附近病因性突变的连锁标记，与冠状动脉疾病、心肌梗死后左心室肥厚和左心室扩张的发生风险增加有关。我们在一个基于人群的特发性充血性心力衰竭患者队列中调查了这种血管紧张素转换酶基因型与死亡率之间的关联。
从一大群未经选择的充血性心力衰竭患者（n = 2711）中招募了193名患者，测定其基因型。对患者进行超声心动图检查，并在随访5年后获得生存数据。通过类似程序对来自普通人群的对照组（n = 77）进行了研究。
研究组和对照组中D等位基因的频率无显著差异（0.57对0.56，p = 无显著性差异）。DD基因型患者的长期生存率明显低于其余患者（5年生存率49%对72%，对数秩检验评估p = 0.0011）。多变量Cox比例风险分析证实了DD基因型对预后的独立重要性，死亡率与DD基因型的比值比为1.69（95%置信区间1.01至2.82）。两组心脏功能数据的唯一显著差异是DD组左心室质量指数增加（153±57对134±44 g/m2，p = 0.019）。
血管紧张素转换酶基因DD多态性与特发性心力衰竭患者较差的生存率及左心室质量增加有关。结果提示血管紧张素转换酶基因多态性、血管紧张素转换酶活性、心肌肥厚和生存率之间可能存在病理生理途径。因此，DD基因型可能是充血性心力衰竭患者预后不良的一个标志物。
